Intermediate vitamin D derivatives with reactive groups at C-20 are widely used in synthesizing vitamin D derivatives with use, or potential use, in different therapeutic fields, for example: bone metabolism diseases, diseases characterized by altered cell differentiation and proliferation (dermatology and oncology), etc.
The chemistry of both closed and open cycle system steroids is complex due to the simultaneous combination in the molecules of different functionalization and several chiral centers, therefore there is a special interest in reactions and reactants that allow greater selectivity and specificity in the reaction products.
European patent application EP78704-A1 discloses intermediates for the synthesis of vitamin D derivatives with general formulas:
Wherein, among many other possibilities, R′ and R″ may represent an optionally substituted alkylidene group. However, said patent application does not disclose a single specific case of a compound in which said positions configure a double bond substituted with a single halogen atom. Furthermore, the aforementioned intermediates are prepared by means of a Wittig reaction on the aldehyde precursor.
Patent application WO92/03414-A discloses the compound 1(S),3(R)-bis-tert-butyldimethylsilyloxy)-20(R)-(2,2-dichlorovinyl)-9,10-seco-pregna-5(E),7(E),10(19)-triene as an intermediate for obtaining vitamin D analogues having at least one triple bond in the side chain at C-20 (the corresponding dibrominated derivative is also claimed), and the article by Calverley et al. (Bioorganic Medicinal Chemistry Letters), Vol. 3, No. 9, pp. 1841-1844 (1993) discloses the compound of formula (V) (corresponding 20(S) isomer) for the same purpose as the alkyne precursor.

Although structurally similar to the monohalogen derivatives object of this invention, these dihalogenated compounds are actually different in their structure, in their synthesis and in their reactivity, since from dihalogenated compounds it is very difficult to obtain halogen-free alkenes in a single step, which can be easily obtained from monohalogenated compounds. Nor have mono- or diiodoalkenyl derivatives been disclosed, which are considered to be more interesting due to the greater reactivity of iodine.
The authors of the present invention have found that new useful compounds having a monohalovinyl group as a side chain joined at C-20 allow a new synthesis route that is able to provide pharmacologically useful vitamin D derivatives with better efficiencies and greater stereoselectivity, methodological simplicity and fewer byproducts and impurities. For example, these alkenyl monohalo derivatives are susceptible to being used for preparing a wide variety of organometallic compounds by substitution of the halogen with a metal, which are satisfactorily used to form new C—C bonds.
Therefore, the object of the present invention are new compounds useful for obtaining vitamin D derivatives having a monohalovinyl group as a side chain joined at C-20.
A process for preparing said compounds further belongs to the object of the present invention.